Drug's lasting benefits sees breast cancer deaths down by third

Oxford researchers used data from 20 trials comparing tamoxifen use for five years against no tamoxifen. Credit: US National Cancer Institute

The benefits of using tamoxifen to prevent recurrence of breast cancer after surgery continue to accrue long after women stop taking the drug, a study led by Oxford University has found.

The findings suggest that for women with the most common type of breast cancer, full compliance with daily tamoxifen therapy for five years would reduce the long-term chances of dying by at least a third.

"Breast cancer is a nasty disease because it can come back years later," says Dr. Christina Davies of the Clinical Trial Service Unit at Oxford University, and one of the lead investigators. "This study now shows that tamoxifen produces really long-term protection.

Most breast cancers are oestrogen receptor (ER)-positive  in the US or UK, its about 4 out of 5 breast cancers that are ER-positive.

Since tamoxifen acts on the ER protein in breast cancer cells, it can have an effect only if those cells contain some ER protein. But a simple test on surgically removed breast cancers can determine whether the cancer is ER-positive or not.

Various treatments can be given after apparently successful breast cancer surgery to prevent any tiny residual fragments eventually causing the cancer to come back as an incurable disease.

Many randomized trials have been conducted to try to determine the best treatment options, and every 5 years for the past 25 years the Early Breast Cancer Trialists Collaborative Group (EBCTCG) has brought together all the evidence from all of these trials.

In the current study, funded by Cancer Research UK, the Medical Research Council and the British Heart Foundation, the researchers brought together individual patient data for over 20,000 women with early-stage breast cancer from 20 randomised trials. The trials compared treatment with tamoxifen for 5 years against no tamoxifen, with participants showing 80% compliance in taking the daily pill.

Most of the trials of tamoxifen began in the 1980s, meaning there is now lots of data available on the long-term effects of treatment after women stopped taking the drug. That long-term analysis, published in the Lancet medical journal, now reveals large additional benefits of tamoxifen in reducing breast cancer deaths, not only during the first decade but also during the second decade after treatment began.

The researchers found that in women with ER-positive disease, 5 years of daily tamoxifen safely reduced the long-term (15-year) risks of breast cancer recurrence and death. It was effective whether or not chemotherapy had been given.

Remarkably, the researchers found a highly significant reduction in breast cancer mortality, not only during the five years of treatment and the five years following, but also during years 1014.

Even in weakly ER positive disease, tamoxifen substantially reduced the likelihood of the cancer recurring.

There is a newer class of drugs called aromatase inhibitors (AIs) that offer an alternative to tamoxifen for some patients, but AIs are effective only in post-menopausal women.

Dr. Davies explains that tamoxifen was developed 50 years ago and is long out of patent, so is relatively cheap. But even if costs are ignored it remains a major first-line treatment option for women with ER-positive breast cancer, she says  especially for women pre-menopause.

Moreover, the rare life-threatening side-effects of tamoxifen (uterine cancer and blood clots) are mainly experienced by women over 55 years of age, so there is little risk from giving tamoxifen to younger women.

Worldwide, half of all new patients diagnosed with breast cancer are younger than 55 years  thats 0.7 million women.